Cancer Research and Treatment

Genitourinary cancer

Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment: Jaewon Hyung, Hyung-Don Kim, Gi Hwan Kim, Yong Mee Cho, Yeon-Mi Ryu, Sang-Yeob Kim, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee; Cancer Res Treat. 2024;56(2):624-633. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1076

Abstract PDF Supplementary Material PubReader ePub: Purpose
Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype.
Materials and Methods
Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population.
Results
A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1–expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02).
Conclusion
Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.

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Lung and Thoracic cancer

Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples: Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee; Cancer Res Treat. 2022;54(3):737-743. Published online September 24, 2021; DOI: https://doi.org/10.4143/crt.2021.773

Abstract PDF Supplementary Material PubReader ePub

Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

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Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy
Shuai Wang, Yongsen Wang, Xuan Wu, Li Yang, Xiaoju Zhang
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Clinicopathologic features of histologic transformation in lung adenocarcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitors
Halim Song, Deokhoon Kim, Se Jin Jang, Hee Sang Hwang, Joon Seon Song
Annals of Diagnostic Pathology.2025; 77: 152478. CrossRef
Whole Exome Sequencing Study Identifies Distinct Characteristics of Transformed Small Cell Lung Cancer With EGFR Mutation Compared to De Novo Small Cell and Primary Non‐Small Cell Lung Cancers
Jinjing Tan, Dan Zhao, Qunhui Wang, Yanjing Peng, Jie Li, Xi Li, Nanying Che, Ying Hu, Hua Zheng
Cancer Medicine.2025;[Epub] CrossRef
Clinical application of microwave ablation combined with coaxial needle biopsy using different sequences for treating lung nodules suggestive of malignancy
Yibing Li, Xinyou Su, Ruobing Li, Jianqiang Zhao, Aimei Ouyang, Taiyang Zuo
International Journal of Hyperthermia.2025;[Epub] CrossRef
Using ex vivo bioengineered lungs to model pathologies and screening therapeutics: A proof‐of‐concept study
Mohammadali Ahmadipour, Jorge Castilo Prado, Benyamin Hakak‐Zargar, Malik Quasir Mahmood, Ian M. Rogers
Biotechnology and Bioengineering.2024; 121(10): 3020. CrossRef
Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome
Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
Cancer Research Communications.2024; 4(7): 1738. CrossRef
Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases
Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
Journal of Clinical Medicine.2023; 12(4): 1411. CrossRef
Gene‐level dissection of chromosome 3q locus amplification in squamous cell carcinoma of the lung using the nCounter assay
Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
Thoracic Cancer.2023; 14(26): 2635. CrossRef
Clinical Outcome of Stereotactic Body Radiotherapy in Patients with Early-Stage Lung Cancer with Ground-Glass Opacity Predominant Lesions: A Single Institution Experience
Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
Cancer Research and Treatment.2023; 55(4): 1181. CrossRef
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Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
Frontiers in Oncology.2022;[Epub] CrossRef

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Phase II Study of Topotecan and Etoposide as Second-line Treatment in Chemotherapy-refractory Small-cell Lung Cancer: Chul Kim, Joo Hyuk Sohn, Joo Hang Kim, Se Kyu Kim, Young Sam Kim, Joon Chang, Jae Yong Cho; Cancer Res Treat. 2002;34(5):334-338. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.334

Abstract PDF

PURPOSE
Refractory small-cell lung cancer (SCLC) has a poor prognosis, and current salvage chemotherapy for refractory SCLC, such as CAV (cyclophosphamide, adriamycin, vincristine) or topotecan, has an unsatisfactory outcome, with a response rate and overall survival of less than 10% and 6 months, respectively. This phase II study evaluated the role of topotecan combined with etoposide in SCLC patients that have progressed, or relapsed, within 3 months following completion of the initial chemotherapy.
MATERIALS AND METHODS
Twenty-seven patients were entered into this study. Eligible patients had an ECOG performance status of less than, or equal to, 2, at least one bidimensionally measurable lesion and adequate end organ function. IV topotecan, 1.0 mg/m2/d for 5 consecutive days, and etoposide, 100 mg/m2/d through days 1 to 3, were administered every 3 weeks until disease progression or undue toxicity.
RESULTS
The major toxicity was myelosuppression. Grade 3/4 anemia, granulocytopenia, and thrombocy-topenia occurred in 14.2, 34.8, and 27.3% of cycles, respectively. There was no treatment-related death, and other non-hematologic toxicities were generally mild. Four patients achieved partial responses, with a response rate RR of 14.8%. The progression-free survival PFS ranged from 1 to 7 months, with a median of 2.0 months (95% confidence interval 1.22~2.78 months). Twenty-five patients died, with a median overall survival of 5.5 months (ranging from 1 to 21 months, 95% CI 4.32~6.68 months), and the 6-month survival rate was 32.1% (95% confidence interval 14.4~49.8%).
CONCLUSION
The combination of topotecan and etoposide chemotherapy showed a modest response rate, but failed to prolong survival of refractory SCLC patients compared to topotecan monotherapy.

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Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea
Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Lung Cancer: Targets and Therapy.2024; Volume 15: 149. CrossRef

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Primary Gastric Small Cell Carcinoma: Heung Rae Min, Yeon Myung Shin, Seung Do Lee, Sung Do Lee, Bang Hur; J Korean Cancer Assoc. 1999;31(1):188-193.

Abstract PDF: Small cell carcinoma is derived from APUDcells of any parts of the body. Usually the cases are discovered in the lungs and have poor prognosis. Small cell carcinoma has been increasingly reported in various organ outside the lungs, such as the larynx, thymus, esophagus, stomach, pancreas, uterine cervix, and prostate. Primary small cell carcinoma of the stomach is extremly rare. The histology of the tumor was similar to that of ordinary small cell carcinoma of the lung, and the secretory granules were identified by electron microscopy. We report a patient with gastric pure small cell carcinoma who treated by a radical total gastrectomy and chemotherapy.

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TGF-beta-1 Expression and p53 Mutation in Non-small Cell Carcinomas of the Lung: Han Kyeom Kim, Seol Hee Park, Young Soon Na, Yong Gu Kang, Young Sik Kim, Jung Ho Han, Mee Ja Park, Insun Kim; J Korean Cancer Assoc. 1997;29(6):1022-1031.

Abstract PDF: PURPOSE
TGF-beta-1 is actually a major growth inhibitor for most cell types. We assumed that the loss of TGF-beta-1 would be occurred during carcinogenesis of the lung. Also, the mutation and expression of p53 have been known to be major moleclar change of non-small cell carcinoma of the lung. So, the relationship between the mutation of p53 and the expression of TGF-beta-1 in the non-small cell carcinomas were evaluated.
MATERIALS AND METHODS
In 43 non-small cell carcinoma and normal tissue of the lung, their TGF-beta-1 mRNA were measured by RT-PCR and p53 was studied by SSCP and Western blotting assay.
RESULTS
p53 mutation rate in non-small cell carcinomas of the lung (48.4%) was much more frequent than the normal control group (14.3%). The expression rate of TGF-beta-1 in lung carcinomas, especially squamous cell carcinoma (71.4%), was much higher than the normal control group (42.9%). p53 mutation and TGF-beta-1 mRNA in the lung carcinomas were not strongly correlated.
CONCLUSION
It suggests that high expression rate of TGF-beta-1 and p53 mutation are associated with carcinogenesis of non-small cell carcinoma of the lung. High expression rate of TGF-beta-1 in the lung carcinomas can be partly explained by the fact that TGF-beta-1 have capacity to control the production of many components of the extracellular matrix and enhance angiogenesis in favor of tumor growth despite of their inhibitory effects of cell growth. However, additional research is required to determine the exact role of TGF-beta-1 in carcinogenesis of the lung.

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Small Cell Carcinoma with Two Paraneoplastic Syndromes: Dong Il Park, You Hern Ahn, In Soon Kim; J Korean Cancer Assoc. 1994;26(4):657-665.

Abstract PDF: The production of hormones by nonendocrine tumors with resultant clinical syndromes secondary to hormone excess is a well-recognized concomitant of neoplasia. Approximately 15 hormones have been reported to be ectopically secreted by more than 20 different tumor types. Although small cell carcinoma of the lung produces a wide variety of peptide hormones including ADH, ACTH and related fragments, calcitonin and serotonin, ectopic production of ADH and corticotropin are seen most frequently. The simultaneous presence of both syndromes has been reported in the literature only several occasians. We experienced a case of small cell carcinoma of the lung with two paraendocrine syndromes. A 53-year-old man was seen at the nephrology department of Hangyang University Hospital on Jan#. 29, 1994. His history was significant for 3 months of hunger pain, peripheral edema and muscle weakness. He had no history of previous illness except for l month duration of mild hypertension. On physical examination, 3 cm sized right supraclavicular lymph node was palpable with a blood pressure of 150/l00 mmHg. He had no truncal obesity or abnormal skin pigmentation. Initial laboratory studies showed the following values: sodium, 109 mEq/l: potassium, 3.7 mEq/l; chloride, 91 mEq/l; bicarbonate, 22.5 mEq/l; glucose, 229 mg/dl. A diagnosis of the SIADH was considered because of the hyponatremia and the euvolemic status of the patient. The serum osmolarity was 233 mosm/kg with a less-than dilute urine osmolarity of 260 mosm/kg & 24-hour urinary sodium excretion was 104 mEq/day. Results of thyroid studies were within normal limits. The biopsy of right supraclavicular lymph node revealed metastatic small cell carcinoma. A diagnosis of ectopic ACTH production was persued to explain the development of hypertension, hyperglycemia and peripheral edema. 24-hour urine for free cortisol level was 186 pg/day (normal 10~80pg/day) & an AM ACTH level (281 pg/ml, normal, 20~100 pg/ml) was high in the presence of high cortisol level (25.69 ug/dl). Results of computed tomography of the chest showed a small mass in the right lower lobe with invasion to right inferior pulmonary vein and left atrium along with metastatic lesions in the left lobe of the liver.

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A Case of Concurrent Occurrence of Small Cell Carcinoma and Adenocarcinoma in the Stomach: Ki Nam Shim, Sa Young Park, Sun Young Lee, Jin Hyuk Choi, Soon Nam Lee, Woon Sup Han; J Korean Cancer Assoc. 1995;27(3):513-521.

Abstract PDF: Frimary small cell careinoma of the stomach is an extremely rare disease. It has similar clinical behavior with small cell cardnoma of lung, which shows aggressive course with rapid and wide dissemination and very poor prognosis. We report a case of concurrent occurrence of primary small cell carcinoma and adeno- carcinoma in the stomach with multiple intraaMominal metastases, which had responded to combination chemotherapy with 5-FU, VP-16, and Cisplatin.

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Pimary small Cell Carcinoma of the Esophagus: Kyung Ho Chang, Sung Ki Kim, Jong Woon Ahn, Ho Sik Choo, Eun Hoo Hong, Mi Young Park, Kyung Tae Park; J Korean Cancer Assoc. 1995;27(5):879-887.

Abstract PDF: Small cell carcinoma of the esophagus is a rare tumor. There has been about 180 cases world-widely and 7 cases in Korea since McKeown reported the first 2 cases of small cell carcinoma of the esophagus in 1952. Small cell carcinoma of the esophagus has a poor prognosis because of rapid progress and widespread dissemination such as small cell carcinoma of the lung. So it can be regarded as a systemic disease, and multimodality treatment including chemotherapy should be used. Using small cell lung cancer as a model, limited disease patients should receive multimodality therapy including chemotherapy followed by surgery and/or radiation and extensive disease patients receive chemotherapy only. Here we report the study of a 52-year-old male patient with primary small cell carcinoma of esophagus metastasized to liver and left supraclaviculer lymph node. We treated him with a multi-drug regimen (VP-16, ifosfamide and cisplatin) being used in small cell carcinoma of the lung at our hospital After two cycles of combination chemotherapy, the primary and metastatic lesions. as evaluated by esophagoscopy, barium esophagogram and abdominal CT scan, had markedly improved, and we evaluated as partial response. And we will treat him with four more cycles of chemotherapy.

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